August 9, 2017

Credit: CC0 Public Domain

Can chemicals that are added to breakfast cereals and other everyday products make you obese? Growing evidence from animal experiments suggests the answer may be "yes." But confirming these findings in humans has faced formidable obstacles - until now.

A new study published today in Nature Communications details how Cedars-Sinai investigators developed a novel platform and protocol for testing the effects of chemicals known as endocrine disruptors on humans.

The three chemicals tested in this study are abundant in modern life. Butylhydroxytoluene (BHT) is an antioxidant commonly added to breakfast cereals and other foods to protect nutrients and keep fats from turning rancid; perfluorooctanoic acid (PFOA) is a polymer found in some cookware, carpeting and other products; and tributyltin (TBT) is a compound in paints that can make its way into water and accumulate in seafood.

The investigators used hormone-producing tissues grown from human stem cells to demonstrate how chronic exposure to these chemicals can interfere with signals sent from the digestive system to the brain that let people know when they are "full" during meals. When this signaling system breaks down, people often may continue eating, causing them to gain weight.

"We discovered that each of these chemicals damaged hormones that communicate between the gut and the brain," said Dhruv Sareen, PhD, assistant professor of Biomedical Sciences and director of the Induced Pluripotent Stem Cell Core Facility at the Cedars-Sinai Board of Governors Regenerative Medicine Institute. "When we tested the three together, the combined stress was more robust."

Of the three chemicals tested, BHT produced some of the strongest detrimental effects, Sareen said.

While other scientists have shown these compounds can disrupt hormone systems in laboratory animals, the new study is the first to use human pluripotent stem cells and tissues to document how the compounds may disrupt hormones that are critical to gut-to-brain signaling and preventing obesity in people, Sareen said.

"This is a landmark study that substantially improves our understanding of how endocrine disruptors may damage human hormonal systems and contribute to the obesity epidemic in the U.S.," said Clive Svendsen, PhD, director of the institute and the Kerry and Simone Vickar Family Foundation Distinguished Chair in Regenerative Medicine. More than one-third of U.S. adults are considered to be obese, according to federal statistics.

The new testing system developed for the study has the potential to provide a much-needed, safe and cost-effective method that can be used to evaluate the health effects of thousands of existing and new chemicals in the environment, the investigators say.

For their experiments, Sareen and his team first obtained blood samples from adults, and then, by introducing reprogramming genes, converted the cells into induced pluripotent stem cells. Then, using these stem cells, the investigators grew human epithelium tissue, which lines the gut, and neuronal tissues of the brain's hypothalamus region, which regulates appetite and metabolism.

The investigators then exposed the tissues to BHT, PFOA and TBT, one by one and also in combination, and observed what happened inside the cells. They found that the chemicals disrupted networks that prepare signaling hormones to maintain their structure and be transported out of the cells, thus making them ineffective. The chemicals also damaged mitochondria - cellular structures that convert food and oxygen into energy and drive the body's metabolism.

Because the chemical damage occurred in early-stage "young" cells, the findings suggest that a defective hormone system potentially could impact a pregnant mother as well as her fetus in the womb, Sareen said. While other scientists have found, in animal studies, that effects of endocrine disruptors can be passed down to future generations, this process has not been proved to occur in humans, he explained.

More than 80,000 chemicals are registered for use in the U.S. in everyday items such as foods, personal care products, household cleaners and lawn-care products, according to the National Toxicology Program of the U.S. Department of Health and Human Services. While the program states on its website that relatively few chemicals are thought to pose a significant risk to human health, it also states: "We do not know the effects of many of these chemicals on our health."

Cost and ethical issues, including the health risk of exposing human subjects to possibly harmful substances, are among the barriers to testing the safety of many chemicals. As a result, numerous widely used compounds remain unevaluated in humans for their health effects, especially to the hormone system.

"By testing these chemicals on actual human tissues in the lab, we potentially could make these evaluations easier to conduct and more cost-effective," Sareen said.

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12 comments

The political/corporate bias in nutritional science is beyond belief. It is a well known fact that carbs like bread, pasta,potatoes, rice, sugar and corn are the real cause of heart disease, diabetes and weight gain. For years we have been brainwashed to view fats as the problem when in reality we should be getting 70% of our calories from fats including animal fats and oils.

Faulty science is no accident, it is bought and paid for by interested parties.

The political/corporate bias in nutritional science is beyond belief. It is a well known fact that carbs like bread, [...] 70% of our calories from fats including animal fats and oils.

Faulty science is no accident, it is bought and paid for by interested parties.

Right you are, "MR" sticky sick --the same interests that have brainwashed you to the above dietary catechism of "pseudoscientific mjumbo, and most likely pays you per post to try to disseminate this dangerous and antiscience whole cloth of lies.

As far as the corporate bias in nutritional science, you are absolutely correct, and --as in so many other areas-- the corporate takeover is very nearly 100% complete.

Since you didn't bother to comment upon the content of the article, please allow me to do so now:

Countless animal studies have established these effects. The pervasiveness of these compounds in human tissue is also known, so this is only a very limited first step,

in establishing actual effects in humans, and almost certainly unnecessary given animal studies--but so be it.

As to why they chose these particular compounds for study...that would be anyone's guess, since there are several other well-know endocrine disrupting and/or carcinogenic compounds in ubiquitous use that are feared to be much more potent that the three in this study.

All that aside, it is already pretty well established that these types of chemicals produce a pretty wide range of effects in animal studies, and therefore it is very likely that most of these effects are produced in humans, as well, namely: obesity, metabolic disorder, phenotypic changes, sexual disorder/dysfunction, carcenogenicity.... quite a long list.

It is no mere coincidence that, at the same time that all of these compounds have come into widespread use(and are also widespread environmental toxins) that the incidence of these types of disorders in humans and animals has ballooned.

Cost and ethical issues, including the health risk of exposing human subjects[...]numerous widely used compounds remain unevaluated in humans for their health effects, especially to the hormone system."By testing these chemicals on actual human tissues in the lab, we potentially could make these evaluations easier to conduct and more cost-effective," Sareen said.

This is unfortunate, indeed, as it may have established a bar that is so high that it will take centuries to penetrate the legal armor of corporate greed and remove these chemicals from use. And all based upon the simple fact that humans and animals are not EXACTLY the same -even when possessing 99.99% OF THE SAME GENOME. Therefore:

While other scientists have found, in animal studies, that effects of endocrine disruptors can be passed down to future generations, this process has not been proved to occur in humans, he explained.

The green movement spends vast sums of money fighting those who feed the world and then complain that the poor are starving. Of course they blame the wealthy for the starvation. As an example look at the false DDT scare and the millions that were killed as a result. That falsehood was not accidental the data was purposely falsified.

In the end, we are interrupting evolution in ways we don't understand yet; possibly both good and bad. Obviously these compounds aren't killing anybody right after exposure, so this isn't at the forefront of research or thought. Humans evolved for millions of years without exposure to anything like Bispehnols, Phthalates, Triclosan, Glyphosate, the chemicals mentioned here (BHT, PFOA, and TBT), and thousands of other compounds. Only in the past couple hundred years have we seen environmental introduction. I doubt we will ever know the full extent of evolutionary disruption since there are so many variables involved. Our bodies are amazing in what they can handle, but constant exposure to low levels of so many new man-made chemicals can't be good over the long term.

Given the newish research into the gut microbiome, I'm really interested in how everything is affecting the little bugs that live in our stomachs.

Riley before we started messing with modern farming, chemistry and fossil fuels the average age of death was just over 60 or so. Thus the overall cost/benefit ratio of our tampering seems to be a giant positive.

MR166, yes, I would agree with you that as far as life span goes, our tampering has had a positive overall effect....on a macro level. I'm more talking about the micro.

For example, one could say that antibiotics have been one of the greatest inventions of mankind. They have helped with adding years to our lifespan. Penicillin won its developers a nobel prize in medicine. Overall, I'd say a positive effect. But after the development of them, did we have the foresight to know that being non-selective in what microbes we are trying to extinguish, and overuse, would cause the microbes to evolve and cause antibiotic resistance. We also didn't think ahead and just added antimicrobials to everyday products such as hand soaps. Only recently has Triclosan been banned in soap. Water treatment plants don't get rid of these, along with other chemicals. Would constant exposure to low doses not only change evolutionary direction for us, but also any soil, water, etc. microbes?

The green movement spends vast sums of money fighting those who feed the world and then complain that the poor are starving. [...] and the millions that were killed as a result. That falsehood was not accidental the data was purposely falsified.

If, by "those who feed the world", you mean the Corporate Food Industry, then the above comment could be taken somewhat seriously.

Except for the DDT bit. that is complete horseshit.

As for the Corporate Food Industry- you would do well to join the greens in combating those vampires, both for the health and safety of you and your family -and for the rest of the people who have little other option but to eat the products they produce.

Also, it would be nice if you included the rest of the world when you speak a generality like "those who feed the world", because your beloved "those who feed the world" don't feed a goddam single person that doesn't have the $$$ to pay for the poison first.

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